Inhibition of Lymphangiogenesis and Hemangiogenesis in Corneal Inflammation by Subconjunctival Prox1 siRNA Injection in Rats

Rho, Chang Rae; Choi, Jun-Sub; Seo, Minkoo; Lee, Suk Kyeong; Joo, Choun‐Ki

doi:10.1167/iovs.14-14433

Cited by 17 publications

(8 citation statements)

References 39 publications

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“…18, 19 It has been shown that with a temporary insult to the cornea, the outgrowth of blood vessels and lymphatic vessels occurs as early as 2 days and peaks around day 14. Thereafter, regression of lymphatics starts earlier and is more pronounced than that of blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease

et al. 2016

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Purpose The human orbit is an environment that is vulnerable to inflammation and edema in the setting of autoimmune thyroid disease. Our study investigated the tenet that orbital adipose tissue lacks lymphatic vessels and analyzed the clinicopathologic differences between patients with acute and chronic thyroid eye disease (TED). The underlying molecular mediators of blood and lymphatic vessel formation within the orbital fat were also evaluated. Design Retrospective cohort study Participants The study included fat specimens from 26 orbits of 15 patients with TED undergoing orbital decompression. Orbital fat specimens from patients without TED as well as cadaveric orbital fat served as controls. Methods Tissue specimens were processed as formalin-fixed paraffin-embedded sections (FFPE) or frozen cryosections for immunohistochemistry. Total RNA was extracted and analyzed via quantitative (real-time) reverse transcription polymerase chain reaction (qRT-PCR). Clinicopathological correlation was made by determining the Clinical Activity Score (CAS) of each patient with TED. Main Outcome Measures Samples were examined for vascular and lymphatic markers including podoplanin, LYVE-1, and CD31 by immunohistochemistry, as well as for mRNA levels of VEGF, VEGF receptors, SEMA-3F, NRP-1, NRP-2, podoplanin and LYVE-1 by qRT-PCR. Results Clinicopathological correlation revealed increased staining of CD31-positive blood vessels in patients with acute TED with CAS > 4, as well as rare staining of podoplanin-positive lymphatic vessels within acutely inflamed orbital fat tissue. Additionally, qRT-PCR analysis demonstrated increased expression of vascular endothelial growth factor receptor 2 (VEGFR-2) as well as VEGF signaling molecules: VEGF-A, VEGF-C, and VEGF-D. Conclusions In acute TED, compared to chronic TED and control orbital fat, there is increased blood vessel density suggesting neovascularization and rare lymphatic vessels suggestive of limited lymphangiogenesis. This pro-angiogenic and pro-lymphangiogenic microenvironment is likely due to the increased expression of VEGFR-2 and VEGF-A, VEGF-C, and VEGF-D. These findings imply that orbital edema in acute TED may be mediated, in part, by both the formation of new, immature blood vessels and the formation of lymphatic capillaries that are functionally incapable of draining interstitial fluid.

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Section: Discussionmentioning

confidence: 99%

Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease

et al. 2016

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“…Subconjunctival injection of Prox1 siRNA significantly inhibited alkali burn‐induced lymphangiogenesis and hemangiogenesis in the cornea compared with negative control. Prox1 siRNA downregulated the expression of LYVE‐1, podoplanin, VEGFR2, and VEGFR3 …”

Section: The Drug Treatment Of Cnvmentioning

confidence: 99%

Recent drug therapies for corneal neovascularization

Liu

Wang

et al. 2017

Chem Biol Drug Des

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Corneal neovascularization (CNV) is a common pathological change in ocular surface diseases. It is not only the factor that affects vision but also the main cause for corneal graft failure. Based on the mechanism of CNV, many achievements have been developed to suppress the formation of CNV. There are certain novel drugs such as aflibercept, gold nanoparticles, and netrins which provide us with new clues to treat CNV. However, we still need to develop more effective therapeutic drugs. It is of great significance to develop new effective drugs to suppress the occurrence of CNV. In this paper, recent drug therapies for CNV are reviewed. The electronic database (PubMed) is searched for relative basic research and randomized clinical trials that are published recently.

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“…VEGFC is the main prolymphangiogenic factor that acts through activating its cognate receptor, VEGFR3, expressed on lymphatic endothelial cells. 21,36 qRT-PCR analysis shows that all of the detected representative proangiogenic and prolymphangiogenic cytokines were temporarily downregulated following performing the CXL protocol. The downregulated proangiogenic and prolymphangiogenic cytokines include VCAM-1, CD31, VEGFR2, VEGFR3, VEGFC, and LYVE-1.…”

Section: Discussionmentioning

confidence: 99%

“…This image analysis system was modified based on previous studies. [21][22][23] Photographs were analyzed in a random order by two double-blinded investigators to minimize observer bias.…”

Section: Corneal Neovascularization Assaymentioning

confidence: 99%